Toxic effects of organophosphates on nerve cell growth and ultrastructure in culture

Abstract

Organophosphates (OP) comprise one of the major classes of pesticides in use today. It is well accepted that the primary site of action of the OPs is at cholinergic synapses. However, it has been suggested that OPs may have direct neural effects as well. In this study, cultured chick dorsal root ganglia (DRC) were used to study the effect of fenthion (FEN), an OP pesticide, on isolated nerve cell growth and ultrastructure. Light microscopic evaluation revealed a dose‐response relationship between the concentration of FEN (10⁻² M to 10⁻⁵ M) and severity of morphologic changes. Cultured ex‐plants were treated with a lower concentration of FEN (10⁻⁶ M) and morphologic alterations were compared to those observed in explants treated with 10⁻⁶ M paraoxon, a more acutely toxic OP, or 10⁻⁶ M neostigmine, a non‐OP inhibitor of acetyl‐cholinesterase. Based on both light and electron microscopy, neostigmine had no observed effect on cell morphology except for an inhibition of the extension of neurites by DRG cells. In contrast, explants treated with OPs exhibited a significant alteration in cell morphology. Initial lesions were observed first in the neurites and pseudo‐podia and consisted of vacuolization, loss of tubular structures, retraction of pseudopodia, and cell membrane disruption at the growth cone. Lipid accumulations were observed within the cytoplasm of treated cells. The effects of paraoxon on DRG cell morphology were significantly more severe than the effects of FEN, and lipid vacuoles observed in paraoxon‐treated cells were several times larger than those observed in FEN‐treated cells (5–10 μm in diameter vs. 0.5–1.0 μm in diameter). Results show that OPs have a direct effect on DRG nerve cells in culture, consistent with an alteration in cell membrane integrity. Cultured DRG cells can be useful in the evaluation of toxicologic effects.